Verma Nandini, Chaudhury Indrajit, Kumar Deepak, Das Rakha H
Institute of Genomics and Integrative Biology, Delhi, India.
FEBS Lett. 2009 Sep 3;583(17):2968-74. doi: 10.1016/j.febslet.2009.08.007. Epub 2009 Aug 14.
Persistently elevated level of TNF-alpha has been implicated in several inflammatory disorders, however, its autocrine production through TNF-alpha receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-alpha expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-alpha induced NF-kappaB activation to a higher extent. It was further observed that NF-kappaB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-alpha expression. All these results suggest that TNF-alpha expression is regulated by synergistic signaling of TNF receptors through downstream NF-kappaB activation.
TNF-α水平持续升高与多种炎症性疾病有关，然而，其通过TNF-α受体信号进行的自分泌产生机制却知之甚少。在此我们报告，在脂多糖（LPS）刺激的THP-1巨噬细胞中，用脱氧核酶或小干扰RNA（siRNA）同时沉默TNF受体R1和R2，比单独沉默它们能更有效地抑制TNF-α表达。同时沉默TNF受体也能更大程度地抑制TNF-α诱导的NF-κB激活。进一步观察到，NF-κB抑制剂而非c-Jun氨基末端激酶抑制剂（SP600125）可抑制TNF-α表达。所有这些结果表明，TNF-α表达受TNF受体通过下游NF-κB激活的协同信号调控。
